Synthesis and crystal structure of 2-[(2,3,5,6-tetrafluoropyridin-4-yl)amino]ethyl methacrylate

In the crystal structure of the title compound, the packing is driven by C—H⋯F, N—H⋯O and C—H⋯π contacts. Hirshfeld surface analysis showed that the largest contribution to the surface contacts arise from F⋯H/H⋯F interactions.


Chemical context
Perfluoropyridine (C 5 NF 5 ; PFPy) is an ideal candidate to use in the preparation of complex fluorinated compounds and materials as PFPy is reactive towards nucleophilic addition (Sandford, 2012). Furthermore, our group and others have demonstrated that this addition can be regio-selectively controlled, with stoichiometric addition to the 4-(para-) position being exclusive with a broad range of nucleophiles (Brittain & Cobb, 2019;Peloquin et al., 2020;Seyb & Kerres, 2013). Sequential addition can also be accomplished at the 3,5-(meta-) positions (Corley et al., 2019;Houck et al., 2021). As part of our ongoing work in this area, the synthesis and single-crystal structure of the title compound, C 11 H 10 F 4 N 2 O 2 , is reported herein.

Structural commentary
The title compound ( Fig. 1) crystallizes in the monoclinic space group P2 1 /n with one molecule in the asymmetric unit. The N2-C6 bond is rotated by only 15.81 (8) from the C1-C5/N1 ring plane, presumably to encourage conjugation of the nitrogen atom lone pair with the aromatic ring system, which is reflected in the C3-N2 bond length of 1.3522 (16) Å ; the C3-N2-C6-C7 torsion angle is À81.68 (16) . The amine nitrogen atom (N2) and ester oxygen atom (O1) are gauche to one another, with N2-C6-C7-O1 = 61.84 (13) . The C10 methyl group is oriented in such a fashion as to enable a weak C-HÁ Á Á interaction with the aromatic ring of an adjacent molecule (Table 1).

Supramolecular features
The main directional interactions in the crystal structure of the title compound are of the type C-HÁ Á ÁF, N-HÁ Á ÁO and C-HÁ Á Á (Table 1). The N-HÁ Á ÁO hydrogen bonds link the molecules into [010] chains, with adjacent molecules related by a 2 1 screw axis. Weak hydrogen-bonding interactions are observed between one hydrogen atom bound to each carbon atom of the two-carbon (C6/C7) linker unit between the amine nitrogen atom and the ester, and F3 as acceptor. One of these interactions is intramolecular (C6-H6AÁ Á ÁF3) with the other being intermolecular (C7-H7AÁ Á ÁF3). A hydrogen-bonding interaction occurs between the secondary amine and the carbonyl oxygen atom (N2-H1N2Á Á ÁO2). Finally, a weak C-HÁ Á Á interaction is observed between H7B and the pyridine ring system.
Hirshfeld surface analysis was used to investigate the presence of hydrogen bonds and intermolecular interactions in the crystal structure. The Hirshfeld surface analysis (Spackman & Jayatilaka, 2009) and the associated twodimensional fingerprint plots (Spackman & McKinnon, 2002) were generated by CrystalExplorer17.5 (Turner et al., 2017), using standard surface resolution with the three-dimensional d norm surfaces plotted over a fixed color scale of À0.025 (red) to 1.38 (blue) a.u.; the pale-red spots symbolize short contacts and negative d norm values on the corresponding surface plots shown in Fig. 2 Table 1 Hydrogen-bond geometry (Å , ).

Figure 1
The molecular structure of the title compound (a) and the unit-cell packing (b). Displacement ellipsoids are shown at the 50% probability level.

Figure 2
Map of d norm (a) and shape index (b) onto the Hirshfeld surface for the title compound.

Database survey
A search of the November 2019 release of the Cambridge Structure Database (Groom et al., 2016), with updates through November 2012, was performed using the program ConQuest (Bruno et al., 2002). The search was limited to 2,3,5,6-tetrafluoropyridine-based compounds with a secondary amine nitrogen atom bound to the ring in the 4-position. This search resulted in 19 hits: the C-C-N-C torsion angles indicate planarity, presumably due to conjugation of the nitrogen atom lone pair into the pyridine ring system, in the majority of cases. In cases of non-planarity, this is typically due to steric factors of the substituent on the nitrogen atom or conjugation of that nitrogen lone pair into the system of the substituent. For example, in CSD refcode NIXMEN (Ranjbar-Karimi et al., 2008), the bulk of a phenyl ring attached to the nitrogen atom subsitutent discourages planarity, resulting in a torsion angle of 37.4 . In TAPRAD (Yamaguchi et al., 1992), the conjugation of the nitrogen lone pair is into a urea substituent, vice the pyridine ring, with a torsion angle of 38.7 .

Synthesis and crystallization
2-[(Perfluoropyridin-4-yl)amino]ethan-1-ol was synthesized using a known method and used without further purification (Peloquin, et al., 2020). Methacryloyl chloride was purchased from Sigma and distilled under reduced pressure prior to use.
A 500 ml round-bottom flask equipped with an addition funnel was charged with 2-[(perfluoropyridin-4-yl)amino]ethan-1-ol (13.4 g, 62.3 mmol), trimethylamine (10.7 ml, 77.2 mmol) and diethyl ether (300 ml). The solution was stirred under nitrogen at 273-278 K for 15 minutes. Next, a solution of methacrylol chloride (7.50 ml, 76.8 mmol) in ether (10 ml) was added dropwise to the round-bottom flask using an addition funnel. The solution was allowed to gradually warm to room temperature and was stirred for 96 h under nitrogen. Precipitated salts were removed by vacuum filtration and the filtrate was concentrated under reduced pressure. Crystals of the title compound in the form of colorless needles were obtained by recrystallization from a solution in warm ($328 K) hexanes (

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 3. N-bound H atoms were refined freely. C-bound H atoms were positioned geometrically (C-H = 0.95-0.99 Å ) and refined as riding with U iso (H) = 1.2-1.5U eq (C).

Figure 3
The overall two-dimensional fingerprint plot for the title compound.

2-[(2,3,5,6-Tetrafluoropyridin-4-yl)amino]ethyl 2-methylprop-2-enoate
Crystal data Special details Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.